Should antigen-antibody rapid diagnostic tests be used to detect acute HIV infection? A systematic review and meta-analysis of diagnostic performance

Introduction Prompt HIV diagnosis is essential to enabling effective prevention and treatment, thereby interrupting transmission and sustain epidemic control. Strategies that could diagnose individuals during acute HIV infection (AHI), while leveraging standard systems that deliver same visit results, have potential to further enhance impact. Antibody-only (Ab) rapid diagnostic tests (RDTs), which are unable to detect AHI, remain the global standard, particularly in resource-limited settings. Antigen-antibody (Ag/Ab) RDTs have been available for more than a decade, however, their use has been largely limited to high-income settings and their ability to detect AHI in resource-limited settings remains unclear. Methods We systematically searched six databases through November 2024 for studies evaluating Ag/Ab RDTs vs laboratory reference standards in individuals aged ≥18 months. Outcomes included diagnostic accuracy, patient-level outcomes, and implementation. Risk of bias was assessed with QUADAS-2, JBI Critical Appraisal and ROBINS-I tools. Diagnostic accuracy was meta-analyzed with a bivariate random-effect model; other outcomes were synthesized narratively. Results From 1,366 screened records, 53 studies from 24 countries were included. The pooled sensitivity of Ag/Ab RDTs for AHI was only 48% (95% CI: 34–62) with specificity of 97% (95% CI: 84–100). Analytical sensitivity (detection of p24 antigen) was 31% and antibody detection was 15%. Ag/Ab RDT sensitivity was higher in studies using serum/plasma specimens (66%) or in laboratory setting (54%) and compared to studies using fingerstick/capillary or venous blood (33–35%). Among oral PrEP users, Ag/Ab RDTs sensitivity was 25% (95% CI, 13–44) and specificity of 94% (95% CI, 64–99). HIV positivity varied widely across population. Uptake, feasibility and linkage were generally favourable, although challenges in resource-limited settings were noted. Discussion Ag/Ab RDTs appear to have limited ability to detect AHI, missing more than half of AHI cases, especially in resource-limited-settings and when using fingerstick/whole blood samples and implemented within PrEP programmes. Further research should evaluate cost-effectiveness, feasibility, and implementation under real-world conditions in resource-limited contexts. Conclusions Detection of AHI using Ag/Ab RDTs remains a challenge. Programmes should continue to prioritize maintaining flexible, low-cost testing strategies aligned with WHO guidance to maximize access and impact, based on their setting and context.